The principal aims are to gain a broader understanding of the pathophysiology of immune hemolysis, particularly autoimmune hemolysis, and to determine the relationship of these phenomena to coexisting malignant disease. The work will be concerned with: 1) The preparation, characterization and clinical evaluation of anti-complement antiglobulin reagents of different specificities (e.g. anti-Cl, C2, C4, C3A, C3d, C5, C6). Emphasis will be placed on defining the specificities most appropriate for diagnostic vs cross-matching use, with provisional guidelines for standardization of such reagents. 2) Evaluation of in vitro rosette formation as a useful index in classification and management of autoimmune hemolytic anemia (AHA). 3) Study of possible cross-reactivity of red cell antigens with tumor antigens, with particular emphasis upon the cross-reactivity of carcinoembryonic antigen (CEA) extractable from colon carcinomas and anti-CEA antibodies with human red cell antigens (particularly blood group A). Similar studies will be extended to tumor specific antigens extractable from bronchigenic carcinoma. 4) Studies of cold agglutinins, including their incidence in non-lymphoreticular malignancies, in autoimmune diseases (not primarily hematologic) and in pregnancy, as well as studies of 7S IgM cold reactive agglutinins in sera and as a minor fraction after SS reduction of 19S IgM cold agglutinins. 5) Studies of the incidence of autoantibodies of multiple immunoglobulin classes (IgG, IgA, IgM) in eluates from red blood cells sensitized in sera containing high titer cold agglutinins, and in sera and eluates from red cells of patients with warm AHA. 6) Participation in a collaborative study of the incidence of HLA sensitization in patients who have received transfusions only of previous frozen, thawed processed donor red blood cells.